Huyghe, Jon and Priem, Dario and Van Hove, Lisette and Gilbert, Barbara and Fritsch, Juergen and Uchiyama, Yasuo and Hoste, Esther and van Loo, Geert and Bertrand, Mathieu J. M. (2022) ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway. SCIENCE, 378 (6625). pp. 1201-1207. ISSN 0036-8075, 1095-9203
Full text not available from this repository. (Request a copy)Abstract
Cell death induced by tumor necrosis factor (TNF) can be beneficial during infection by helping to mount proper immune responses. However, TNF-induced death can also drive a variety of inflammatory pathologies. Protectives brakes, or cell-death checkpoints, normally repress TNF cytotoxicity to protect the organism from its potential detrimental consequences. Thus, although TNF can kill, this only occurs when one of the checkpoints is inactivated. Here, we describe a checkpoint that prevents apoptosis through the detoxification of the cytotoxic complex IIa that forms upon TNF sensing. We found that autophagy-related 9A (ATG9A) and 200kD FAK family kinase-interacting protein (FIP200) promote the degradation of this complex through a light chain 3 (LC3)-independent lysosomal targeting pathway. This detoxification mechanism was found to counteract TNF receptor 1 (TNFR1)-mediated embryonic lethality and inflammatory skin disease in mouse models.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; EMBRYONIC LETHALITY; LIVER DEGENERATION; AUTOPHAGY; DEATH; IMMUNODEFICIENCY; PHOSPHORYLATION; DEFICIENCY; ACTIVATION; APOPTOSIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Krankenhaushygiene und Infektiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2024 10:52 |
| Last Modified: | 01 Feb 2024 10:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58073 |
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